{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T19:37:36Z","timestamp":1783021056251,"version":"3.54.6"},"posted":{"date-parts":[[2026,6,30]]},"group-title":"Neurology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,30]]},"abstract":"<jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Dementia, particularly Alzheimer\u2019s disease (AD), is a major global health challenge, with prevalence projected to reach 150 million cases by 2050. AD is characterized by progressive cognitive decline linked to neuroinflammation and neurodegeneration. Non-steroidal anti-inflammatory drugs (NSAIDs) have been explored as potential neuroprotective agents, particularly diclofenac, which has been proposed to modulate microglial inflammasome signaling. However, prior studies investigating NSAIDs in AD have yielded inconsistent findings. We therefore reexamined the relationship between selected NSAIDs and dementia outcomes in a large longitudinal cohort from the National Alzheimer\u2019s Coordinating Center (NACC).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We analyzed cross-sectional and longitudinal data from the NACC database collected between 2005 and 2022. Associations between NSAID exposure and dementia, AD, and cognitive trajectories were examined. Propensity score matching was performed to compare NSAID users with matched non-users while adjusting for demographic and clinical confounders. Longitudinal mixed-effects models were used to assess cognitive decline based on Montreal Cognitive Assessment (MoCA) scores.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Among 47,165 participants, diclofenac and naproxen use were associated with a lower prevalence of dementia and AD compared with matched non-users, whereas etodolac showed no significant associations. Diclofenac users demonstrated reduced odds of dementia and AD. Naproxen showed similar cross-sectional associations. In longitudinal modeling, diclofenac users had a significantly slower rate of cognitive decline than non-users.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>These findings suggest a compound-specific association between NSAID use and AD, with diclofenac potentially modulating disease progression through anti-inflammatory mechanisms. The observed modulation of longitudinal cognitive decline supports further investigation of inflammatory pathways, including microglial and inflammasome signaling, as therapeutic targets in biomarker-defined AD populations.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.27.26355593","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:15:29Z","timestamp":1782854129000},"source":"Crossref","is-referenced-by-count":0,"title":["NSAID use is associated with lower dementia and Alzheimer\u2019s disease prevalence and slower cognitive decline: A retrospective longitudinal analysis of the NACC cohort"],"prefix":"10.64898","author":[{"given":"Carolin Luisa","family":"Hoehne","sequence":"first","affiliation":[{"name":"Department of Neurology, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Bonhoefferweg 3, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Salinas","sequence":"additional","affiliation":[{"name":"Rocky Mountain Movement Disorders Center, Englewood, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afsaneh","family":"Shirani","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Marion Bloch Neuroscience Institute, Kansas City, MO, USA"},{"name":"Department of Neurology, University of Missouri-Kansas City, Kansas City, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Stuve","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Peter O\u2019Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Neurology Section, Dallas VA Medical Center, 4500 South Lancaster Road, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Elena","family":"Stopschinski","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Peter O\u2019Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Center for Alzheimer\u2019s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070211300917000_2026.06.27.26355593v1.1","first-page":"3","article-title":"Epidemiology of Dementia: The Burden on Society, the Challenges for Research","volume":"1750","year":"2021","journal-title":"Biomark Alzheimers Dis Drug Dev"},{"key":"2026070211300917000_2026.06.27.26355593v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"2026070211300917000_2026.06.27.26355593v1.3","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.8522"},{"key":"2026070211300917000_2026.06.27.26355593v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"2026070211300917000_2026.06.27.26355593v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30037-6"},{"key":"2026070211300917000_2026.06.27.26355593v1.6","doi-asserted-by":"publisher","DOI":"10.1177\/17562864231156674"},{"key":"2026070211300917000_2026.06.27.26355593v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109720"},{"key":"2026070211300917000_2026.06.27.26355593v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14945"},{"key":"2026070211300917000_2026.06.27.26355593v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24160"},{"key":"2026070211300917000_2026.06.27.26355593v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1769-z"},{"key":"2026070211300917000_2026.06.27.26355593v1.11","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7393"},{"key":"2026070211300917000_2026.06.27.26355593v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01155-w"},{"key":"2026070211300917000_2026.06.27.26355593v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.10.016"},{"key":"2026070211300917000_2026.06.27.26355593v1.14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.639369"},{"key":"2026070211300917000_2026.06.27.26355593v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116232"},{"key":"2026070211300917000_2026.06.27.26355593v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02743.x"},{"key":"2026070211300917000_2026.06.27.26355593v1.17","unstructured":"Ghlichloo I , Gerriets V. 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